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RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohens Kappa = 0.47 ± 0.07; P

BACKGROUND: Acute lung allograft dysfunction (ALAD) is an imprecise syndrome denoting concern for the onset of chronic lung allograft dysfunction (CLAD). Mechanistic biomarkers are needed that stratify risk of ALAD progression to CLAD. We hypothesized that single cell investigation of bronchoalveolar lavage (BAL) cells at the time of ALAD would identify immune cells linked to progressive graft dysfunction. METHODS: We prospectively collected BAL from consenting lung transplant recipients for single cell RNA sequencing. ALAD was defined by a ≥10% decrease in FEV1 not caused by infection or acute rejection and samples were matched to BAL from recipients with stable lung function. We examined cell compositional and transcriptional differences across control, ALAD with decline, and ALAD with recovery groups. We also assessed cell-cell communication. RESULTS: BAL was assessed for 17 ALAD cases with subsequent decline (ALAD declined), 13 ALAD cases that resolved (ALAD recovered), and 15 cases with stable lung function. We observed broad differences in frequencies of the 26 unique cell populations across groups (p = 0.02). A CD8 T cell (p = 0.04) and a macrophage cluster (p = 0.01) best identified ALAD declined from the ALAD recovered and stable groups. This macrophage cluster was distinguished by an anti-inflammatory signature and the CD8 T cell cluster resembled a Tissue Resident Memory subset. Anti-inflammatory macrophages signaled to activated CD8 T cells via class I HLA, fibronectin, and galectin pathways (p

Background: It remains challenging to quantify lung pharmacokinetics (PK) of a drug administered and targeted to act in the lung. Exhaled breath particles (PEx), which are generated when collapsed distal airways reopen during inhalation, offer a noninvasive way to access undiluted epithelial lining fluid (ELF). Therefore, it was the aim of this study to investigate whether PK data can be derived from PEx. Methods: Six healthy volunteers received either an inhaled dose (400 µg) or an oral dose (8 mg) of salbutamol in a randomized, crossover design with 7-day washout between treatments. PEx were collected before and at nine time points after dosing (0–315 minutes [min]). Following each 15 min PEx sampling period, nasosorption and plasma samples were collected. Salbutamol was quantified by liquid chromatography-mass spectrometry. Results: After oral delivery and inhalation, salbutamol PK profiles could be obtained for plasma and nasal samples. In PEx samples, a PK profile could be obtained in 5 of 6 participants after inhalation, but the salbutamol concentration was often at or below detection limit after oral intake. After inhaled administration we found higher salbutamol concentrations in PEx as compared with nasal and plasma samples. Conclusion: This study provides proof of principle that PEx samples can be used to quantify drug levels in ELF. [ABSTRACT FROM AUTHOR]

A 40-year-old man with chronic myeloid leukemia presented to the hospital with recurrent dyspnea and hypoxemic respiratory failure. He presented from his outpatient transplant infectious diseases appointment with dyspnea, cough, worsening hypoxemia, acute kidney injury, and somnolence after discharge from the hospital 2 weeks prior with a similar presentation. During the previous hospital stay, he underwent bronchoscopy and alveolar lavage with negative infectious workup. He was prescribed caspofungin, amphotericin, and continued posaconazole for prior probable invasive fungal infection (elevated blood BD-glucan and pulmonary nodules). Antibiotics included previous meropenem for esophageal nocardiosis, cefepime and azithromycin during admission, and now ceftriaxone for nocardiosis in the outpatient setting for convenience of home infusion. He was prescribed diuretics for presumed volume overload. Despite home diuretics, antimicrobials, and supplemental oxygen, he re-presented with worsening symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Accuracy of diagnostic tests for invasive pulmonary aspergillosis (IPA) using bronchoalveolar lavage fluid (BALF) remains suboptimal. Elevated tissue iron in lung transplant and murine models is linked to invasive Aspergillus growth. This study examines the correlation between BALF iron levels, IPA, and 12-week mortality. Methods: We conducted a retrospective cohort study at a tertiary care center, including 100 BALF samples from patients with hematological malignancies and suspected IPA between 2014 and 2019. Data regarding iron concentrations, mycological tests, and 12-week mortality were analyzed. Results: Higher iron levels correlated with a greater likelihood of IPA based on EORTC/MSGERC 2020 definitions (p = 0.038). The ROC area was 0.648 (95% CI 0.531-0.764), with an optimal cut-off of 0.75 µmol/L to distinguish cases (27 probable and 0 proven IPA) from controls (56 possible and 17 no IPA), with sensitivity 76.9% and specificity 47.3%. Iron levels were positively correlated with higher fungal loads (galactomannan: Spearman’s ρ 0.323, p = 0.001; Aspergillus PCR Ct-values: ρ − 0.602, p = 0.002). A trend toward higher 12-week mortality was observed in patients with iron concentrations ≥ 0.90 µmol/L compared to lower levels (p = 0.086). Conclusions: BALF iron concentrations were highest in those with probable IPA, followed by possible IPA and lowest in patients without IPA, with higher iron levels also correlating with fungal loads and potentially with 12-week mortality. However, given the various potential confounding factors, further prospective studies are essential to establish causality. These findings warrant additional investigation into BALF iron as a potential marker for 12-week survival, but validation is necessary before considering it as a supplementary marker in the current EORTC/MSGERC 2020 classification for probable or possible IPA. [ABSTRACT FROM AUTHOR]

Background: Severe pulmonary infection is the primary cause of death in children aged < 5 years. The early identification of pathogenic bacteria and targeted anti-infective therapies can significantly improve the prognosis of children with severe infections. This study aims to provide a reference for the rational use of antibiotics at an early stage in children with severe pulmonary infections. Methods: A retrospective, single-center longitudinal study included children with severe pulmonary infections between January 2017 and December 2022 by obtaining their bacterial culture results of bronchoalveolar lavage fluid. Results: This study included 4080 samples. The age of onset for severe pulmonary infection increased annually. The proportion of severe pulmonary infections across the different age groups and years was statistically significant (p < 0.001). Among children with severe pulmonary infections, bacilli were the most prevalent, followed by cocci and fungi. The predominant bacilli were Acinetobacter baumannii and Klebsiella pneumoniae. The predominant cocci identified in this study were Streptococcus pneumoniae and Staphylococcus aureus. The primary fungi included Candida albicans and Aspergillus fumigatus, which showed significant differences (p < 0.05). The incidence of drug-resistant bacteria has gradually declined, with infection rates of multidrug-resistant bacteria and extended-spectrum beta-lactamases consistently decreasing annually. For carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, the infection rates peaked in 2018, with statistical significance (p < 0.001). Conclusions: Severe pulmonary infections in children are significantly associated with age and types of infectious pathogens. Gram-negative bacteria are the primary cause of severe pulmonary infections in children. Clinicians should rationally use antibiotics according to the local distribution and drug resistance of pathogens, thereby enhancing therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Invasive pulmonary aspergillosis (IPA) increases the risk of mortality of critically ill patients. Diagnostic criteria specifically targeting patients in intensive care units(ICUs) have been developed to improve diagnostic sensitivity. This study investigated health outcomes among patients in ICUs with Aspergillus isolates identified using bronchoscopy. Methods: This retrospective cohort study obtained data from the Chang Gung Research Database of Chang Gung Memorial Hospital. Patients admitted to the ICU between January 2017 and December 2022 who received bronchoalveolar lavage were enrolled. Patients with a fungus culture yielding Aspergillus spp. isolates or who had an Aspergillus galactomannan antigen index value of >1.0 were categorized into the Aspergillus-positive group. Results: A total of 2372 patients were enrolled, and 146 patients (6.16%) tested positive for Aspergillus. Of the patients who tested positive for Aspergillus, 37.67% had a positive culture result, and 77.4% had a positive galactomannan antigen result. Patients with Aspergillus isolates were more likely to have a recent influenza infection, concurrent bacterial sepsis, and a cavitation and to die in hospital (in-hospital mortality rate 58.9% vs. 48.57%, P = 0.016). Discussion: Identifying Aspergillus through bronchoscopy in the ICU is associated with higher mortality rates than in patients who test negative for Aspergillus. Galactomannan antigen from bronchoalveolar lavage may provide higher diagnostic sensitivity. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) is a valuable tool for investigating cellular heterogeneity in diseases such as equine asthma (EA). This study evaluates the HIVE™ scRNA-seq method, a pico-well-based technology, for processing bronchoalveolar lavage (BAL) cells from horses with EA. The HIVE method offers practical advantages, including compatibility with both field and clinical settings, as well as a gentle workflow suited for handling sensitive cells. Our results show that the major cell types in equine BAL were successfully identified; however, the proportions of T cells and macrophages deviated from cytological expectations, with macrophages being overrepresented and T cells underrepresented. Despite these limitations, the HIVE method confirmed previously identified T cell and macrophage subpopulations and defined other BAL cell subsets. However, compared to previous studies T helper subsets were less clearly defined. Additionally, consistent with previous scRNA-seq studies, the HIVE method detected fewer granulocytes and mast cells than anticipated in the total BAL samples. Nevertheless, applying the method to purified mast cells recovered an expected number of cells. A small set of eosinophils were also detected which have not been characterized in earlier studies. In summary these findings suggest that while the HIVE method shows promise for certain applications, further optimization is needed to improve the accuracy of cell type representation, particularly for granulocytes and mast cells, in BAL samples. [ABSTRACT FROM AUTHOR]

Glucocorticosteroids remain the most common pharmaceutical approach for the treatment of equine asthma but can be associated with significant side effects, including respiratory microbiome alterations. The goal of the study was to assess the impact of 2% lidocaine nebulization, a projected alternative treatment of equine asthma, on the healthy equine respiratory microbiota. A prospective, randomized, controlled, blinded, 2-way crossover study was performed, to assess the effect of 1 mg/kg 2% lidocaine (7 treatments over 4 days) on the equine respiratory microbiota compared to control horses (saline and no treatment). Clinical assessments and respiratory samples, including nasal wash, endoscopic tracheal aspirate and bronchoalveolar lavage fluid, were obtained at each sample collection timepoint. The profile of the respiratory bacterial microbiota was evaluated using 16S amplicon sequencing, and clinical data compared using related samples analyses, based on data normality. The treatment did not affect the clinical data or alter the tracheal and nasal microbiota in healthy horses. However, time explained 12.6% of microbiota variation among samples. A significant difference in bacterial composition was observed between nasal and tracheal samples, showing the greatest relative abundance of Actinobacteria and Firmicutes, respectively. Bacterial DNA from bronchoalveolar lavage fluid did not amplify with generic primers targeting the V4 variable region of the prokaryotic small subunit ribosomal RNA gene, despite attempting multiple DNA extraction methods and PCR protocols, and after excluding PCR inhibition. This observation indicates that bronchoalveolar lavage fluid of healthy horses has a low bacterial load. [ABSTRACT FROM AUTHOR]

Aims: Asthma is characterized by chronic airway inflammation, persistent cough, wheezing, and dyspnea. This study aimed to evaluate the efficacy of Limosilactobacillus reuteri VHProbi® M07 (M07) administration in alleviate the asthma severity in a mice model. Methods and results: In vitro studies confirmed that M07 can survive and proliferate within the gastrointestinal tract. BALB/c mice were administered M07 both before and after ovalbumin (OVA) challenge. Serum levels of OVA-specific immunoglobulin (Ig) E and IgG1, inflammatory cells and cytokines in bronchoalveolar lavage fluid were assessed, along with histopathological examination of lung tissue. Compared to the placebo (PLA) group, mice treated with M07 exhibited significantly lower levels of OVA-specific IgE and IgG1 (P < 0.01). The counts of eosinophils and neutrophils were also significantly reduced in both the pretreated (PRE) group and post-treated (POS) group compared with the PLA group (P < 0.01). Histological analysis of lung tissues verified the protective effects of M07 against inflammation, demonstrating reduced infiltration of inflammatory cells. Additionally, mice in the PRE and POS groups showed significantly increased levels of IL-10 (P < 0.01), and significantly decreased levels of IL-5, IL-13, MCP-1, eotaxin, and tumor necrosis factor-α (P < 0.01). Conclusions: Oral administration of M07 mitigated key features of inflammatory responses in the OVA-induced mice asthma model. These findings suggest that M07 holds therapeutic potential for the treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Sepsis-induced acute lung injury (ALI) is a severe clinical condition accompanied with high mortality. Tangeretin, which is widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear. Methods: We established an ALI model via intraperitoneally injected with 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied intraperitoneally 30 min before LPS treatment. Dexamethasone (Dex) was used as a positive control. Hematoxylin and eosin (HE) staining and protein content in bronchoalveolar lavage fluid (BALF) were determined to detect the degree of lung injury. RNA-seq was also applied to explore the effect of tangeretin on ALI. In vitro, RAW264.7 were treated with Nrf2 siRNA, the expression of ferroptosis-associated biomarkers, including glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) were assessed. Glutathione (GSH), malondialdehyde (MDA) levels, reactive oxygen species (ROS) and inflammatory factors were also determined both in vivo and in vitro. Furthermore, mice were treated with an Nrf2 inhibitor (ML385) to verify the mechanism of tangeretin in inhibiting sepsis-induced lung injury and ferroptosis. Data were analyzed using one way analysis of variance or two-tailed unpaired t tests. Results: Our study demonstrated that tangeretin significantly alleviated lung injury, reversed the LPS-induced reduction in GPX4 and GSH, and mitigates the elevation of PTGS2 and MDA levels. Tangeretin also reduced 4-HNE and iron levels. Besides, the levels of LPS-stimulated inflammatory factors IL-6, IL-1β and TNF-α were also decreased by tangeretin. RNA-seq and bioinformatics analysis demonstrated that tangeretin inhibited inflammatory response. Mechanistically, we identified that tangeretin inhibited the GPX4-dependent lipid peroxidation through activation of Nrf2. The silence of Nrf2 abolished the inhibitory effect of tangeretin on oxidative stress, inflammatory response and ferroptosis in RAW264.7 cells. Additionally, all the protective effects of tangeretin on ALI were abolished in Nrf2 inhibitor-treated mice. Conclusion: We identified that ferroptosis as a critical mechanism contributing to sepsis-induced ALI. Tangeretin, a promising therapeutic candidate, effectively mitigates ALI through inhibiting ferroptosis via upregulating Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Background Respiratory infections cause a significant amount of morbidity and mortality in pediatric and young adult patients with malignancy. Bronchoscopy with bronchoalveolar lavage (BAL) is frequently utilized in the diagnostic process, but which patients would most benefit is poorly understood. Methods A retrospective study from 2013 to 2022 examined patients with active malignancy who underwent bronchoscopy with BAL. Positive and negative clinical impacts were assessed by 3 independent reviewers according to predetermined criteria. Mixed-effects logistic regression was performed to identify factors associated with positive and negative clinical impact. Results In total, 145 bronchoscopies met inclusion criteria with a median patient age of 12 years (interquartile range 5-17). A total of 30.3% of bronchoscopies had a positive clinical impact with 17.2% leading to a new diagnosis, most commonly Pneumocystis jirovecii pneumonia (PJP) (7.6%). Comparatively, 18.6% had a negative clinical impact, most commonly from a procedural complication (13.1%). Trimethoprim-sulfamethoxazole (TMP-SMX) initiation for treatment of suspected PJP prior to BAL (adjusted odds ratio [aOR] 11.20, 95% CI 1.32-95.29) was associated with positive clinical impact. Requirement for ICU-level care (aOR 18.85, 95% CI 3.60-98.69) or oxygen supplementation by nasal cannula prior to BAL (aOR 18.41, 95% CI 4.78-70.95) were associated with negative clinical impact while prior invasive ventilation (aOR 0.09, 95% CI 0.01-0.58) was associated with the absence of negative clinical impact. Conclusions Patients with potential respiratory infections with high clinical suspicion for PJP who had been started on treatment TMP-SMX prior to BAL benefit most from bronchoscopy with BAL. Patients intubated prior to BAL who were deemed clinically safe for bronchoscopy tolerated the procedure better than those in the ICU not requiring intubation or those requiring supplemental oxygen via nasal cannula. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis, remains a significant global health concern. Targeted Next-Generation Sequencing (tNGS) has emerged as a rapid and comprehensive diagnostic tool for tuberculosis, offering advantages over traditional methods and serving as an effective alternative for drug susceptibility testing and the detection of drug-resistant tuberculosis. OBJECTIVE: This study aimed to retrospectively analyze the clinical characteristics of pulmonary tuberculosis patients. After explore the application value of targeted next-generation sequencing technology in this patient population, providing valuable insights for clinical diagnosis and treatment. METHODS: In this retrospective study, we analyzed data from 65 patients with laboratory-confirmed tuberculosis admitted to Tianjin Baodi Hospital from November 14, 2020, to February 1, 2023. Patients underwent bronchoalveolar lavage fluid (BALF) testing, including acid-fast staining, culture, and tNGS. Biopsies and histopathological examinations were performed on some patients, along with comprehensive radiological assessments for all. RESULTS: Among the 65 pulmonary tuberculosis patients, targeted next-generation sequencing detected pathogens in bronchoalveolar lavage fluid with a positivity rate of 93.8%, significantly higher than traditional methods such as acid-fast staining, culture, and pathology. Compared to bronchoalveolar lavage fluid smear, targeted next-generation sequencing demonstrated significantly higher diagnostic sensitivity (98.46% vs. 26.15%) and accuracy (98.46% vs. 26.15%). CONCLUSION: Targeted next-generation sequencing, with its high sensitivity and specificity compared to traditional methods, provides unique advantages in detecting pathogens among these patients, highlighting its importance in disease management. [ABSTRACT FROM AUTHOR]

Macrophage (Mph) polarization and functional activity play an important role in the development of inflammatory lung conditions. The previously widely used bimodal classification of Mph into M1 and M2 does not adequately reflect the full range of changes in polarization and functional diversity observed in Mph in response to various stimuli and disease states. Here, we have developed a model for the direct assessment of Mph from bronchial alveolar lavage fluid (BALF) functional alterations, in terms of phagocytosis activity, depending on external stimuli, such as exposure to a range of bacteria (E. coli, B. subtilis and L. fermentum). We have employed polymeric mannosylated ligands (the "trapping ligand") specifically targeting the CD206 receptor to selectively isolate activated Mph from the BALF of patients with pulmonary inflammatory conditions: primary ciliary dyskinesia (PCD), pneumonia and bronchial asthma. An "imaging ligand" allows for the subsequent visualization of the isolated cells using a sandwich technique. Five model strains of E. coli, MH-1, JM109, BL21, W3110 and ATCC25922, as well as B. subtilis and L. fermentum strains, each exhibiting distinct properties and expressing red fluorescent protein (RFP), were used as a phagocytosis substrate. Fluorometric, FTIR- and confocal laser scanning microscopy (CLSM) assessments of the phagocytic response of Mph to these bacterial cells were performed. Mph absorbed different strains of E. coli with different activities due to the difference in the surface villosity of bacterial cells (pili and fimbriae, as well as signal patterns). In the presence of other competitor cells (like those of Lactobacilli), the phagocytic activity of Mph is changed between two and five times and strongly dependent on the bacterial strain. The relative phagocytic activity indexes obtained for BALF-Mph in comparison with that obtained for model human CD206+ Mph in the M1 polarization state (derived from THP-1 monocyte cultures) were considered as a set of parameters to define the Mph polarization profile from the BALF of patients. Mannan as a marker determining the selectivity of the binding to the CD 206 mannose receptor of Mph significantly inhibited the phagocytosis of E. coli and B. subtilis in cases of pneumonia, suggesting an important role of CD206 overexpression in acute inflammation. Conversely, L. fermentum binding was enhanced in PCD, possibly reflecting altered macrophage responsiveness in chronic lung diseases. Our approach based on the profiling of Mph from patient BALF samples in terms of phagocytosis for a range of model bacterial strains is important for the subsequent detailed study of the factors determining dangerous conditions and resistance to existing therapeutic options. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute lung injury (ALI) is an inflammatory disorder affecting patients in intensive care with high mortality. No specific pharmacological treatment is available. Musa paradisiaca L. (banana) is a cosmopolitan plant, and homemade syrup from its inflorescence is used in many countries to treat pulmonary inflammation. Therefore, this study analyzed the hydroalcoholic extract (HEM) of the inflorescence on the ALI experimental model. Methods: Swiss mice were challenged with lipopolysaccharide and treated with HEM after 1, 24, and 48 h (five animals/group, three times). Results: The HEM-treated ALI mice presented a decrease in neutrophil migration in the bronchoalveolar lavage fluid (BALF), in the alveolar region, and in the blood, correlating to downregulation of CD18 expression. The HEM treatment also reduced the protein concentration in the BALF, caused lung edema formation, impaired NF-κB activation via inhibition of TLR4 signaling pathway, and decreased IL-1β, TNF-α production, free DNA release, and myeloperoxidase (MPO) activity. However, the extract induced an increased IL-10 in the BALF. Conclusions: Therefore, HEM's anti-inflammatory and immunomodulatory activities in ALI mice are by deactivating neutrophils by decreasing CD18 receptor, free DNA release, and MPO activity and inducing IL-10 production. Thus, this study supports the use of banana inflorescence in folk medicine and suggests its rational use to develop a phytomedicine to treat pulmonary inflammation. [ABSTRACT FROM AUTHOR]

In this study, the anti-inflammatory effect of the hot water extract of Endarachne binghamiae (EB-WE), a type of marine brown algae, was investigated in LPS-stimulated RAW 264.7 cells and an acute lung injury (ALI) mouse model induced by intranasal LPS administration. Treatment with EB-WE significantly inhibited NO and pro-inflammatory cytokine (TNF-a and IL-6) production in LPS-stimulated RAW 264.7 cells. In mRNA analysis, the expression of pro-inflammatory cytokines, COX-2, and iNOS mRNAs, was down-regulated by EB-WE treatment. The phosphorylation of MAPK, IkB, and PI3K/AKT molecules responsible for signal pathways during inflammation in LPS-stimulated macrophages was also significantly inhibited by EB-WE. In an in vivo model for ALI, oral administration of EB-WE significantly reduced the level of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and chemokines (MCP-1, CXC-16, CXCL1, and TARC) in serum or bronchoalveolar lavage fluid (BALF) of mice. Similarly to the results in LPS-stimulated RAW 264.7 cells, treatment with EB-WE significantly inhibited intracellular signal pathways mediated by MAPK, IkB, and PI3K/AKT in lung tissues of mice with ALI, and also decreased the expression of mRNAs of inflammatory mediators such as TNF-a, IL-6, iNOS, and COX-2. Furthermore, the inhibitory effect of EB-WE on ALI was apparently confirmed in histological examination through lung tissue staining. Taken together, it is clear that EB-WE has potential activity to effectively ameliorate the inflammatory responses in macrophages through down-regulation of MAPK, NF-kB, and PI3K/AKT activation, and suppress acute lung injury induced by LPS. These findings strongly suggest that EB-WE is a promising natural product beneficial for developing preventive treatments and cures of inflammation-related diseases. [ABSTRACT FROM AUTHOR]

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary pathology characterized by the accumulation of surfactant within type II alveolar epithelial cells. Whole lung lavage is the standard treatment for pulmonary alveolar proteinosis involving a large volume of fluid is infused into one lung and subsequently retrieved while the other lung is remains ventilated. Fast-tracking a patient undergoing whole lung lavage requires vigilant monitoring of arterial blood gases, fluid status, and respiratory mechanics. We report a case of a patient who underwent whole lung lavage for PAP, where early extubation was performed, avoiding the complications associated with prolonged mechanical ventilation. [ABSTRACT FROM AUTHOR]

A 32-year-old Chinese woman with a cough and bloody sputum was diagnosed with chronic eosinophilic pneumonia. After starting corticosteroid therapy, chest radiography showed improvement in the bilateral infiltrative shadow. However, chest image findings showed worsening of the bilateral infiltrative shadow and pulmonary cavities during the 20 mg/day of oral prednisolone therapy. Transbronchial lung biopsy and bronchoalveolar lavage were repeated, and the patient was diagnosed with pulmonary paragonimiasis. After starting praziquantel treatment, chest radiography findings and clinical symptoms improved. Careful follow-up during corticosteroid therapy is important to judge whether transient improvement and true deterioration of radiological findings. [ABSTRACT FROM AUTHOR]

Background: The lungs are the main organs affected by the systemic granulomatous disease sarcoidosis, which has an unclear etiology. Computerized tomography is now the mainstay for diagnosis and monitoring of pulmonary sarcoidosis. For diagnosis, bronchoalveolar lavage fluid (BALF) is useful since a ratio of cluster of differentiation 4 (CD4)/CD8 T cells greater than 3.5 is predictive of sarcoidosis. Aim: Assess the relationship between the baseline clinical, spirometric, radiological characteristics and the BALF results in patients with newly diagnosed pulmonary sarcoidosis. Patients and methods: This is a cross-sectional analytic study comprising 56 patients (aged >18 years) who had just been diagnosed with pulmonary sarcoidosis and were admitted to the Chest Department of Kasr Alainy Hospital at Cairo University. Spirometric tests using a flow-volume loop, high resolution computed tomography chest and bronchoalveolar lavage (cellular analysis and CD4/CD8 ratio) were performed. Results: Based on the BALF analysis of all the 56 patients, the lymphocytic BAL was 89.3% and the mean CD4/CD8 was 3.3 ± 1.95 (0.65–9.43). The BALF and clinical data correlate well, with lymphocytic BAL being more strongly linked to dyspnea (93.6%) and cough (66.7%) than polymorphs BAL with P value 0.046.This alsoo related to spirometric data, where a lower forced expiratory volume in the first second (FEV1) (mean 66.8 ± 11.62) was linked to lymphocytic BAL compared with polymorphs BAL (mean 72.17 ± 3.97) with P value of 0.032. however, there is no correlation with radiological results. Conclusion: The diagnosis of sarcoidosis is supported by BALF analysis but should not be considered diagnostic by itself. Clinical and spirometric results are correlated with it. However, there is no correlation with radiological results. [ABSTRACT FROM AUTHOR]

The standard modality for diagnosis of smoke inhalational injury in burn patients is bronchoscopy with or without bronchoalveolar lavage (BAL). However, the risks associated with these procedures are poorly described in established literature. We sought to investigate the association between diagnostic BAL at admission and the development of pneumonia in burn patients. This retrospective analysis of intubated burn patients studied those who underwent bronchoscopy on admission, comparing patients who received BAL to those who did not. Demographics and baseline characteristics were analyzed using chi-squared or Student's t -test. Unadjusted and multivariable logistic regression studies assessed the effect of admission BAL on the development of pneumonia. Out of the 196 patients who underwent bronchoscopy, 98 met our criteria for analysis. The BAL group was more likely to be male and have a higher grade of abbreviated injury score. Patients who received BAL were more likely to develop pneumonia during the admission in both unadjusted and multivariable logistic regression models. These patients also had a longer hospital length of stay, greater number of ventilator days, and were more likely to undergo second bronchoscopy. These findings associate admission BAL with increased risk of pneumonia during the index hospitalization, suggesting a judicious use of BAL during admission bronchoscopy in burn patients. [ABSTRACT FROM AUTHOR]

Whereas the intranasally delivered influenza vaccines used in children affect transmission of influenza virus in the community as well as reducing illness, inactivated influenza vaccines administered by intramuscular injection do not prevent transmission and have a variable, sometimes low rate of vaccine effectiveness. Although mucosally administered vaccines have the potential to induce more protective immune response at the site of viral infection, quantitating such immune responses in large scale clinical trials and developing correlates of protection is challenging. Here we show that by using mathematical models immune responses measured in the blood after delivery of vaccine to the lungs by aerosol can predict immune responses in the respiratory tract in pigs. Additionally, these models can predict protection from influenza virus challenge despite lower levels of blood responses following aerosol immunization. However, the inclusion of immune responses measured in nasal swab eluates did not improve the predictive power of the model. Our models are an important first step, providing proof of principle that it is feasible to predict immune responses and protection in pigs. This approach now provides a path to develop correlates of protection for mucosally delivered vaccines in samples that are easily accessed in clinical trials. [ABSTRACT FROM AUTHOR]

Background and Objectives: Lower respiratory tract infections are particularly frequent in hematological patients; their early diagnosis and the timely start of targeted therapy are essential. Bronchoalveolar lavage (BAL) can provide a microbiological sample from the lower airways in a minimally invasive way. This study aimed to determine the diagnostic yield of BAL in hematological patients for microbiological purposes and its influence on modifying the therapeutic strategy. Material and Methods: This multicenter, retrospective, observational study included data from 193 consecutive patients from two centers from January 2020 to October 2022. The patients underwent a bronchoscopy with BAL in cases of pulmonary infiltrates suspicious of pulmonary infection. The demographic data, presenting symptoms, level of immunosuppression, chest CT changes, BAL sampling results, and antimicrobiological drug administration were analyzed. Results: Of the 193 procedures, 143 (74.1%) were performed on hospitalized patients, while 50 were performed on outpatients. In 53.9% of the cases, the BAL isolated at least one germ; in particular, if the procedure was carried out within 72 h of presenting symptoms, the probability of isolating the germ increased significantly (74.3%, p = 0.04). Among the isolated germs, 59.4% were viruses, 28.6% were bacteria, and 12% were fungi. The patients with higher immunosuppression and the febrile ones underwent BAL earlier than the patients with mild immunosuppression (p = 0.01) and those with other presenting symptoms (p = 0.0001). BAL positivity led to a change in empirical antimicrobial therapy in 79 out of 104 cases (77% vs. 36.3%; p < 0.001); these data were also confirmed among the hospitalized patients (81% vs. 44%; p < 0.001). The isolation of a pathogen through BAL and the degree of patient immunosuppression negatively influenced patient survival (p < 0.05 and p < 0.01, respectively). Conclusions: BAL is confirmed as a valid approach for evaluating pulmonary infiltrates in hematological patients, given the excellent clinical impact and high diagnostic yield, mainly if performed early after symptom presentation. However, ongoing antimicrobial treatments at the time of BAL may have potentially affected the diagnostic yield of the procedure. [ABSTRACT FROM AUTHOR]

Objective: Mycoplasmas are structurally simple pathogenic microorganisms that can cause a wide range of diseases in humans and animals and conventional antibiotic therapies of fluoroquinolones and tetracyclines are toxic to young children and young animals and macrolide resistance is increasing. In this context, new anti-mycoplasma antimicrobial agents need to be developed. 22–((4-((4-nitrophenyl)acetamido)phenyl)thio)deoxypleuromutilin (compound 16C) is a novel acetamine phenyl pleuromutilin derivative. This study aimed to evaluate its acute toxicity in mice and generate pharmacokinetic and anti-mycoplasma profiles. Methods: The safety of compound 16C was preliminarily evaluated by oral and intramuscular acute toxicity tests and single intravenous and intramuscular pharmacokinetic experiments were performed to obtain its pharmacokinetic profile. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-killing curves reflected the in vitro effects of the compounds against Mycoplasma pneumoniae. Five groups consisted of three treatments for compound 16C (20, 40, and 80 mg/kg), and two treatments for tiamulin (oral and intramuscular 40 mg/kg) were continued for 4 d. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected at the end of treatment (96 h) and 4 days later (192 h) to assess the in vivo anti-mycoplasma and anti-pneumonia effects. ELISA assays were performed to detect IFN-γ, TNF-α, and IL-8 (CXCL1) in BALF. Lung tissues were fixed with 4% paraformaldehyde and sectioned for histopathological assessment. Results: The results show that compound 16C has low toxicity (LD50 > 5,000 mg/kg). Its pharmacokinetic profile is characterized by a short time to maximum concentration (Tmax = 0.24 h), high bioavailability (F = 71.29%), and short elimination half-life (T1/2kel) (intramuscular and intravenous administration was 2.20 and 1.89 h, respectively). Treatment with compound 16C and intramuscular tiamulin reduced the mycoplasma load in mice. Intramuscular compound 16C and tiamulin also inhibited the release of IFN-γ, TNF-α, and CXCL1, decreasing the accumulation of inflammatory cells in the lungs, thereby mitigating lung damage. Conclusion: This study proved that compound 16C has a strong antimicrobial effect against M. pneumoniae , can be rapidly absorbed and has therapeutic efficacy that provides a basis for developing new anti-mycoplasma drugs. [ABSTRACT FROM AUTHOR]

Background: Although previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts of children with pulmonary tuberculosis (PTB). In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of PTB patients using bronchoalveolar lavage fluid (BALF) samples. Methods: A total of 64 participants, comprising 43 pediatric PTB and 21 pediatric pneumonia patients were recruited in the present study. BALF samples were collected from the above participants. Parallel comparisons between mNGS and conventional microbial test (CMT) pathogen detection were performed. Moreover, the diversity and structure of all 64 patients' lung BALF microbiomes were explored using the mNGS data. Results: Comparing to the final clinical diagnosis, mNGS in BALF samples produced a sensitivity of 46.51%, which was lower than that of TB-PCR (55.00%) and Xpert (55.00%). The diagnostic efficacy of PTB can be highly enhanced by mNGS combined with TB-PCR (AUC=0.8140, P <0.0001). There were no significant differences in the diversity either between patients with TB and pneumonia. Positive mNGS pathogen results in pediatric PTB patients significantly affect the β-diversity of the pulmonary microbiota. In addition, significant taxonomic differences were found in BALF specimens from patients with PTB and pneumonia, both of which have unique bacterial compositions. Conclusions: mNGS is valuable in the etiological diagnosis of PTB, and can reveal pulmonary microecological characteristics. For pediatric PTB patients, the mNGS should be implemented early and complementary to CMTs. [ABSTRACT FROM AUTHOR]

Background: Metagenomic next-generation sequencing (mNGS) has emerged as a promising tool in clinical practice due to its unbiased approach to pathogen detection. Its diagnostic performance in pulmonary tuberculosis (PTB), however, remains to be fully evaluated. Objective: This study aims to systematically review and Meta-analyze the diagnostic accuracy of mNGS in patients with PTB. Methods: We conducted a literature search in PubMed (MEDLINE), Web of Science, Cochrane, and EMBASE databases, including studies published up to 2024. Studies comparing the diagnostic accuracy of mNGS with other methods such as Xpert-MTB/RIF and Mycobacteria tuberculosis (MTB) culture using bronchoalveolar lavage fluid (BALF), sputum, and lung biopsy tissue were included. Preclinical studies, review articles, editorials, conference abstracts, and book chapters were excluded. Statistical analysis was performed using Rev-man5, R package metabias, and Stata software. Results: Thirteen studies met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity and specificity of mNGS for PTB were 83% (95% CI: 69–91%) and 99% (95% CI: 92–100%), respectively. Subgroup analyses revealed that in BALF, mNGS demonstrated a pooled sensitivity of 73% (95% CI: 61–82%) and specificity of 98% (95% CI: 92–100%); in the sputum, the pooled sensitivity was 60% (95% CI: 38–87%) with a specificity of 99% (95% CI: 96–100%); and in the lung biopsy tissue, the pooled sensitivity was 71% (95% CI: 38–95%) and the specificity was 98% (95% CI: 93–100%). For Xpert-MTB/RIF, the pooled sensitivity and specificity were 72% (95% CI: 53–85%) and 100% (95%CI: 100–100%), respectively. Subgroup analyses demonstrated that in BALF, Xpert-MTB/RIF exhibited a pooled sensitivity of 69% (95% CI: 53–81%) and a specificity of 100% (95% CI: 77–100%). The pooled sensitivity and specificity of mycobacteria culture were 50% (95% CI: 36–64%) and 100% (95% CI: 83–100%), respectively. Subgroup analyses indicated that in BALF, the pooled sensitivity of mycobacteria culture was 44% (95% CI: 37–52%) with a specificity of 100% (95% CI: 8–100%); in the sputum, the pooled sensitivity was 42% (95% CI: 21–65%) and the specificity was 100% (95% CI: 100–100%). When combining mNGS with Xpert-MTB/RIF, the pooled sensitivity and specificity were 79% (95% CI: 40–97%) and 98% (95% CI: 95–100%), respectively. Conclusion: mNGS demonstrates similar diagnostic accuracy to Xpert-MTB/RIF in PTB and outperforms mycobacteria culture in terms of sensitivity. Furthermore, mNGS exhibits good detection capabilities across various PTB clinical samples. Systematic review registration: PROSPERO CRD42023427586. [ABSTRACT FROM AUTHOR]

Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma. Methods: Wild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17's pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses. Results: Animal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17. Conclusion: In the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT05332834. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effect of lung recruitment using high frequency ventilation versus volume targeted ventilation on duration of intubation as well as its effect on lung inflammation in preterm infants with respiratory distress syndrome. Methods: The study was conducted on a total of 40 preterm infants, 34 weeks gestational age or less, having RDS that needed intubation and mechanical ventilation within the first 72 h after their birth at the NICU of Mansoura University Children's Hospital during the period from July 2020 to July 2022. Infants included were randomly assigned into two groups, Group A who were subjected to LRM using HFOV (20 cases) and Group B who were subjected to LRM using VTV/AC (20 cases). TGF-β1 level was measured in BAL samples of all studied infants at two time points; before lung recruitment maneuver and at day 5 after lung recruitment or just before extubation if extubation occurs earlier than 5 days. Results: Lung recruitment maneuver had no significant effect on time to extubation. Both groups showed no significant difference in rate of prematurity complications nor delta change of TFG-β1 level in tracheal aspirate of those preterm infants measured before lung recruitment and five days after recruitment or at extubation when extubation occurred earlier. Conclusions: Lung recruitment maneuver was not associated with significant difference between both groups of preterm infants. The results obtained from our study, being the first of its kind to compare the effect of lung recruitment, provide a promising research area for further investigations. [ABSTRACT FROM AUTHOR]

Background: Targeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but concerns are also raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients. Methods: 180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively. The concordance between pathogen reports of both methods and the clinical significance among samples with/without known etiology was further evaluated. Results: Overall, both methods displayed high agreement on pathogen reports, as the average percent agreement reached 95.29%. But tNGS presented a slightly higher detection rate per species than mNGS (PWilcoxon=1.212e-05; standard mean difference = 0.2887091), as detection rates for 32 out of 48 species were higher than those of mNGS. Due to limitations of panel coverage, tNGS identified 28 fewer species than mNGS, among which only 3 were considered clinically relevant. In reference to composite reference standard, accuracy, sensitivity, and specificity combining both tNGS and mNGS reached 95.61%, 96.71%, and 95.68%, respectively, while positive prediction value (PPV) was low at 48.13%, which was caused by low agreement regarding opportunistic pathogens. tNGS and mNGS improved the etiology identification in 30.6% (55/180) and 33.9% (61/180) cases, respectively. Conclusion: Collectively, tNGS presented a similar overall performance in pathogen identification compared to mNGS, but outperformed in some pathogens. This study also demonstrated that deployment of tNGS significantly improves etiology identification in routine practice and provides hints for clinical decisions. The low agreement between clinical diagnosis and NGS reports towards opportunistic pathogens implies that adjudication is essential for report interpretation. Finally, We proposed tNGS as a diagnosis option in clinical practice due to its cost-efficiency. [ABSTRACT FROM AUTHOR]

The article explores the production of oncostatin-M (OSM) by human eosinophils and its increased expression in uncontrolled severe asthma. The study found that OSM is associated with asthma severity, lower lung function, and airway inflammation. Blood eosinophils were shown to release OSM when activated, and OSM levels correlated with airway eosinophilia, lung function, and inflammatory mediators in asthma. The research suggests that OSM from activated eosinophils may play a role in asthma pathogenesis and could be a potential target for treatment. [Extracted from the article]

This report describes the case of a 41-year-old male patient complaining of a hacking cough. The patient was treated with a Janus kinase (JAK) inhibitor for psoriasis. Blood tests revealed mild lymphopenia and high levels of serum cryptococcal antigen. Chest computed tomography revealed infection in the lower lobe of the left lung. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed Tropheryma whipplei. Tropheryma whipplei and Cryptococcus antimicrobial therapies were sequentially administered. During follow-up, the patient showed clinical and radiographic improvement. Tropheryma whipplei is an opportunistic Gram-positive rod-shaped bacterium belonging to the family Actinomycetes. Lung involvement is an unusual but classic manifestation of Whipple's disease. This is the first report of pneumonia caused by infection with Tropheryma whipplei complicated by Cryptococcus. To our knowledge, this is the first case report of Tropheryma whipplei infection following the use of JAK inhibitors. Clinicians should be aware of opportunistic infections that can occur during treatment with JAK inhibitors. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILDs) are pathologies affecting the pulmonary interstitium and, less frequently, the alveolar and vascular epithelia. Bronchoalveolar lavage (BAL) is commonly used in ILD evaluation since it allows the sampling of the lower respiratory tract. The prognostic value of BAL cell counts in ILD is unknown. Flow cytometry quantification of lymphocytes and neutrophils in BAL of 1074 real-life consecutive patients were retrospectively correlated with clinical, radiological, anatomopathological, functional/spirometry, and evolutionary data. Cut-offs with predictive value were established at 7% and 5% for lymphocytes and neutrophils, respectively. Three risk stratification groups (Risk-LN) were established: FAVORABLE (lymphocytes > 7% and neutrophils < 5%), INTERMEDIATE (rest of patients), and UNFAVORABLE (lymphocytes < 7% and neutrophils > 5%), showing 75th percentile overall survival (OS) of 10.0 ± 1.4, 5.8 ± 0.6, and 3.0 ± 0.3 years (p < 0.001), respectively. A scoring model combining Risk-LN and the age of the patients with great predictive capacity for OS on fibrotic and non-fibrotic ILDs is proposed. This score is an independent predictive factor (HR = 1.859, p = 0.002) complementary to the fibrosis status (HR = 2.081, p < 0.001) and the type of treatment. Flow cytometry of BAL provides rapid and accurate quantification of lymphocytes and neutrophils, allowing the establishment of a risk score model that is useful in the clinical management of fibrotic and non-fibrotic ILDs from the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background: The tracheobronchial and oral microbiome may be associated with lung cancer, potentially acting as predictive biomarkers. Therefore, we studied the lung and oral bacteriome and virome in non-small cell lung cancer (NSCLC) patients compared to melanoma controls to discover distinguishable features that may suggest lung cancer microbial biomarkers. Methods: In this pilot case-control study, we recruited ten patients with early-stage NSCLC (cases) and ten age-matched melanoma patients (controls) who both underwent tumor resection. Preoperative oral gargles were collected from both groups, who then underwent transbronchoscopic tracheal lavage after intubation. Lung tumor and adjacent non-neoplastic lung were sterilely collected after resection. Microbial DNA from all lung specimens underwent 16S rRNA gene sequencing. Lavage and gargle specimens underwent whole-genome shotgun sequencing. Microbiome metrics were calculated to compare both cohorts. T-tests and Wilcoxon rank sum tests were used to test for significant differences in alpha diversity between cohorts. PERMANOVA was used to compare beta diversity. Results: No clear differences were found in the microbial community structure of case and control gargles, but beta diversity of case and control lavages significantly differed. Two species, Granulicatella adiacens and Neisseria subflava , which are both common oral commensal organisms, appeared in much higher abundance in case versus control lavages. Case lavages also maintained higher relative abundances of other oral commensals compared to controls. Conclusions: Lung lavages demonstrated oral microbiota enrichment in cases compared to controls, suggesting microaspiration and resultant inflammation. The oral commensals Granulicatella adiacens and Neisseria subflava were more abundant in the tracheobronchial lavages of lung cancer versus melanoma patients, implicating these microorganisms as potential lung cancer biomarkers, warranting further validation studies. [ABSTRACT FROM AUTHOR]

Background: Exposure to standard petrodiesel exhaust is linked to adverse health effects. Moreover, there is a mounting request to replace fossil-based fuels with renewable and sustainable alternatives and, therefore, rapeseed methyl ester (RME) and other biofuels have been introduced. However, recent toxicological research has indicated that biodiesel exhaust may also induce adverse health-related events. Aim: To determine whether exposure to 100% RME biodiesel (BD100) exhaust would cause an acute airway neutrophilic recruitment in humans. Methods: Fourteen healthy subjects underwent exposure to diluted BD100 exhaust and filtered air for 1-h, in a blinded, random fashion. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed six hours after exposure. Differential cell counts and inflammatory markers were determined in the supernatant and biopsies were stained immunohistochemically. Results: Compared with filtered air, BD100 exhaust exposure increased bronchial mucosal endothelial P-selectin adhesion molecule expression, as well as neutrophil, mast cell and CD68 + macrophage numbers. An increased influx of neutrophils and machrophages was also seen in BW. Conclusion: Exposure to biodiesel exhaust was associated with an acute airway inflammation that appeared similar to preceding petrodiesel exposure studies. The present findings, together with the recently reported adverse cardiovascular effects after similar biodiesel exposure, indicate that biodiesel is not free of toxicity and may affect human health. [ABSTRACT FROM AUTHOR]

Background: Nocardiosis is an opportunistic infection that has a low prevalence rate, its clinical manifestations are atypical and can be easily misdiagnosed as other diseases. The correct diagnosis and treatment are frequently delayed by various factors. In this case report, we present a pediatric patient with Neuromyelitis Optica Spectrum Disorders who developed Nocardia farcinica pneumonia complicated by pneumocystis jiroveci infection. Case presentation: An 8-year-old girl with chest pain and cough was admitted to the hospital. She suffered from Neuromyelitis Optica Spectrum Disorders and had been taking methylprednisolone and tacrolimus orally for 3 years. She was admitted to the hospital for tests and was diagnosed with acute pneumonia. Despite empiric antibiotic treatment, her condition gradually worsened. Respiratory distress developed, and she needed to use a ventilator for breathing. The symptoms she exhibited led us to suspect the presence of a tumor. Etiological tests later confirmed the co-infection of Nocardia farcinica and Pneumocystis jiroveci. After treatment, the child's lung infection eventually resolved. Conclusion: The Nocardia bacteria and Pneumocystis jiroveci are widely distributed in the environment, possess the capability of systemic dissemination, and exhibit significant resistance to specific treatments. Invasive sampling is frequently necessary for confirming their presence. Timely and accurate diagnosis as well as treatment play a crucial role in patient survival. [ABSTRACT FROM AUTHOR]

Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and postoperative outcomes. In a transplantation model, donor pigs were stratified to either the treated or the nontreated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion (EVLP) before transplantation. Treatment consisted of 3 doses of 2 × 106 cells/kg: one during EVLP and 2 after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO 2 /FiO 2 ratios and reduced incidence of PGD. Repeated injection of lung-specific cell treatment during EVLP and post transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objective • Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods • Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results • A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion • The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application. (Altern Ther Health Med. 2024;30(12):280-285). [ABSTRACT FROM AUTHOR]

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by the accumulation of surfactant/lipoprotein material in the alveoli and subsequent hypoxemic respiratory failure. Whole lung lavage (WLL), a procedure used to physically remove the lipoprotein material from the alveoli, is the first-line treatment for this disease process. Anesthesia providers may infrequently encounter the management of the WLL procedure due to the rarity of the underlying disease process. Pertinent anesthesia considerations for WLL are covered in the following case report. A review of the literature examines the pathophysiology of PAP, the various approaches to WLL, and the physiologic implications of WLL. [ABSTRACT FROM AUTHOR]

Aim: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. Materials and methods: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. Results: In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. Conclusions: Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to assess the impact of Liver X receptors (LXRs) on airway inflammation, airway remodeling, and lipid deposition induced by cigarette smoke and lipopolysaccharide (LPS) exposure in the lung. Methods: Wild mice and LXR-deficient mice were exposed to cigarette smoke and LPS to induce airway inflammation and remodeling. In addition, some wild mice received intraperitoneal treatment with the LXR agonist GW3965 before exposure to cigarette smoke and LPS. Lung tissue and bronchoalveolar lavage fluid were collected to evaluate airway inflammation, airway remodeling and lipid deposition. Results: Exposure to cigarette smoke and LPS resulted in airway inflammation, emphysema and lipid accumulation in wild mice. These mice also exhibited downregulated LXRα and ABCA1 in the lung. Treatment with GW3965 mitigated inflammation, remodeling and lipid deposition, while the deletion of LXRs exacerbated these effects. Furthermore, GW3965 treatment following exposure to cigarette smoke and LPS increased LXRα and ABCA1 expression and attenuated MyD88 expression in wild mice. Conclusion: LXRs demonstrate the potential to mitigate cigarette smoke and LPS- induced airway inflammation, emphysema and lipid disposition in mice. [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and Results: A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated. Conclusion: These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in. [ABSTRACT FROM AUTHOR]

Grape seed procyanidin extract (GSE) is widely used to promote cardiovascular health and has purported anti-inflammatory properties. Chronic inflammation in the lungs caused by environmental toxins such as tobacco smoking plays a pivotal role in lung cancer development. In a modified phase I lung cancer chemoprevention study conducted in heavy active and former smokers using leucoselect phytosome (LP), a standardized grape seed procyanidin extract complexed with soy phospholipids to enhance bioavailability, three months of LP treatment favorably modulated a variety of surrogate endpoint biomarkers, including markers of cell proliferation. In this correlative study, we further analyzed the effects of LP on cytochrome P450 3A4 (CYP3A4) activities by comparing the endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone, respectively, before and after LP treatment and the anti-inflammatory effects of LP in the lung microenvironment of these participants by comparing a profile of inflammatory cytokines and chemokines in matched pre- and post-treatment bronchoalveolar lavage (BAL) fluids. LP treatment did not significantly alter CYP3A4 activity, and three months of LP treatment significantly decreased tumor necrosis factor (TNF), C-C Motif Chemokine Ligand 3 (CCL3) and granzyme B in BAL fluids. Furthermore, post-LP-treatment BAL fluids significantly reduced migration/invasion of various human lung neoplastic cells in vitro. Our findings support the anti-inflammatory effects of GSE/LP in the lung microenvironment and its potential utility for reducing cancerizing forces, as well as driving forces for other common respiratory diseases such as chronic obstructive pulmonary disease and asthma, in the lungs of heavy former and active smokers. [ABSTRACT FROM AUTHOR]

Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, and narrowing, with a risk of life-threatening attacks. Most current treatments primarily consist of inhalable steroids, which are not without adverse effects. Recently, there has been growing interest in alternative approaches to asthma management. In this study, we investigated the anti-asthmatic effects of the non-steroidal compound CycloZ using acute and chronic mouse models of asthma. Allergic reactions were induced with house dust mite (HDM) extract, and CycloZ or fluticasone propionate (FP) was administered orally or intranasally, respectively. CycloZ significantly ameliorated the HDM-induced robust expression of Th2 cytokines in both models. CycloZ also decreased immune cell infiltration into the lungs and reduced IL-4 and IL-13 cytokine levels in bronchoalveolar lavage fluid (BALF). Moreover, CycloZ greatly attenuated the activation of the TLR-4 pathway, which is involved in HDM recognition and signaling. The beneficial effects of CycloZ were comparable to or even superior to the current steroid treatment, FP, suggesting that CycloZ could be a promising new option for asthma therapy. [ABSTRACT FROM AUTHOR]